Courtesy: Dr Manish Agarwal, Hinduja Hospital, Mumbai, India
OSTEOSARCOMA
• Osteosarcoma is defined as a primary malignant bone tumour in which neoplastic cells produce an osteoid matrix (Ewing’s sarcoma does not produce osteoid matrix).
• Most common primary malignant bone tumour of non-hematopoietic origin
• 2nd most common primary malignant bone tumour (most common- multiple myeloma)
• Diagnosis is confirmed by biopsy and HPE
• Histopathological appearance- Tumour cells directly adjacent to osteoid with NO intervening normal osteoblast lining osteoid
• Other components seen in HPE include various cartilage, fibrous tissue, vascular spaces and sheets of small round cells (it is a high-grade malignant feature).
CLASSIFICATION
1. PRIMARY OSTEOSARCOMA
2. SECONDARY OSTEOSARCOMA
Primary Osteosarcoma is subdivided into:
1.INTRAMEDULLARY (95%)
• HIGH GRADE (chondroblastic, fibroblastic etc)
• LOW GRADE (rare)
2. SURFACE OSTEOSARCOMA (5%) (most commonly low grade)
• PAROSTEAL
• PERIOSTEAL
• HIGH GRADE SURFACE
• DEDIFFERENTIATED
CONVENTIONAL OSTEOSARCOMA
• Incidence: 3-5 per million population between 0-24 years of age
• 3- 5 % of childhood cancer
• Age: 10-25 years
• Male: female = 1.43: 1
• Knee is the most common site
• 2nd peak of age 60-75 years common in western population due to secondary osteosarcoma as in Paget’s diseases, but not seen in India and other Asian countries.
HISTOLOGIC SUBTYPES
• Osteoblastic
• Chondroblastic
• Fibroblastic
• Telengiectatic
• Round cell osteosarcoma
• Giant cell rich osteosarcoma
-These subtypes has no prognostic significance, but may produce a diagnostic dilemma
-Telengiectatic osteosarcoma: purely lytic lesion and may look like aneurysmal bone cyst
Histologic classification
• High grade osteogenic sarcoma is composed of pleomorphic malignant cells with large, hyper chromatic nuclei and frequent mitotic figures
• Low grade osteogenic sarcoma is characterized by scarcity of pleomorphic cells and mitotic figures
Low grade intramedullary osteosarcoma
• Rare, grows slowly
• Can dedifferentiate
SURFACE OSTEOSARCOMA (5% of all osteosarcoma)
• Parosteal
• Periosteal
• High grade surface
• Dedifferentiated parosteal
1. PAROSTEAL OSTEOSARCOMA
• Arises directly adjacent to but distinct from the external surface of a bone
• The most frequent site is on the posterior aspect of distal femur
• Low grade surface osteosarcoma
2. PERIOSTEAL OSTEOSARCOMA
• Radiology: Florid periosteal reaction Codmans triangle seen, Onion peel appearance, Hair on end appearance
• Scalloping of bone
• Low to intermediate grade
• Linear streaking at 90 degrees to the surface of bone like thorns along vascular channels
• If we do biopsy we see “well differentiated cartilage tissue with little osteoid “. So Differential diagnosis is chondrosarcoma
3. HIGH GRADE SURFACE OSTEOSARCOMA
• Rapidly growing tumour
• HPE: similar to conventional intermedullary high grade osteosarcoma
• Treatment: similar to conventional intermedullary high grade osteosarcoma
4. DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA
• A high-grade surface OGS
• In long-standing low-grade osteosarcoma, it dedifferentiates
• Prognosis poor
• Poor response to chemotherapy
• Treatment: chemo with surgery as in any conventional osteosarcoma
SECONDARY OSTEOSARCOMA
• Arises in the background of a previous bone disorder such as Paget’s disease, bone infarct, fibrous dysplasia or prior radiation
• Hardly seen in young patients, but it accounts for more than half of patients over 60 years of age
• These high-grade tumours show a poor prognosis and do not respond well to adjuvant therapy
• More common in western population, less common in India
EXTRA SKELETAL OSTEOSARCOMA
• Not related to bone osteosarcoma
• High grade soft tissue sarcoma that forms bone
• Treated like any other high grade soft tissue sarcoma
• No evidence of benefit with chemo
• Treatment: wide excision + RT as in any soft tissue sarcoma.
ETIOLOGY:
• True etiology not known
• No known genetic factors except germ line mutation like p53 or Rb gene mutations
• Radiation coupled with germ line mutations or any preexisting diseases can be a risk factor
– Initial patient evaluation is aimed to access whether the patient’s limb is
• SALVEGABLE
• BORDERLINE
• NON SALVEGABLE
IMAGING
Plain radiograph:
– classic appearance- metaphyseal osteoblastic lesion with “sun burst periosteal reaction” or hair on end appearance + codmans triangle+ permeative ill-defined border + soft tissue extension
– wide range of other presentations may be seen like Lytic/ permeative lesion, moth eaten appearance, diaphyseal location etc
MRI:
– To confirm diagnosis and evaluate the entire bone
– Gives a clue to neurovascular bundle involvement, local extension, joint involvement, extend to other sites of bone, to determine site of biopsy and staging
Staging in osteosarcoma-? done with MRI of bone + Chest x ray + CT chest
CHEST X RAY:
– Useful to detect pulmonary mets
– Detects a metastatic nodule only if > 8mm in diameter
CT CHEST:
– Detects any metastasis as small as 2mm.
– HRCT not required, simple spiral CT with multiple slices will be sufficient.
PET-CT:
– Useful but not yet in guideline
– Always combine with CT chest
– Useful is assessing response and rare mets like lymph node mets
BIOPSY:
– Irrespective of how classic the radiographic appearance is, HPE confirmations is a must prior to treatment
– J needle biopsy is preferred to open biopsy
– Slide review whenever biopsy was done outside
– NO open biopsy except by the team doing the final procedure
TREATMENT OF CHOICE:
• Neoadjuvant chemo + wide or radical resection or amputation followed by adjuvant chemo + pulmonary metastasis resection, if any after neoadjuvant chemo
• Surgery alone with no chemo -15-20% was the 2-year survival rate
• Surgery with chemotherapy has improved the survival rates to, 50-80 % of 2-year survival rate and 60-70% of 5year survival rate
Chemotherapeutic agents in osteosarcoma
– High dose methotrexate
– Adriamycin
– Cisplatinum
– Ifosfamide
NEOADJUVANT CHEMOTHERAPY
o Improved survival by controlling micromets
o Buys time for fabrication of customised joints
o Total 6-9 cycles of which 2-5 cycles are preop
o 3 drugs better than 2
o Acute toxicity risk more with methotrexate
o Permanent sterility with ifosfamide
o Makes limb salvage surgery easier by
• decreasing vascularity
• sterilisation of reactive zone of satellites
• better margination with thicker pseudocapsule
• healing of pathological fractures
-the histological response to chemotherapy is the single most important prognostic factor
-grading is used to allow evaluation of chemo response
- grade 1 – none or minimal
- grade 2 – more than 10% viable tumour
- grade 3 – more than 90% necrosis
- grade 4 – 100% necrosis- no viable tumour
TREATMENT
• Irrespective of response to chemotherapy, surgery is a must to remove all of the disease
• unlike Ewing’s sarcoma, osteosarcoma is radioresistant
• Metastatic diseases if resectable should also be resected
Decision making factors
• Localised or metastatic
• Salvageable or not
• Socioeconomic status (chemotherapy costs, costs of revision, multiple procedures)
AMPUTATIONS
Usually in 10-15 % of patients and indication include
• Large diseases
• Unplanned surgery
• Initially complicated open biopsy
• Extensive soft tissue extension
LIMB SALVAGE SURGERY
Prerequisites include
• Adequate finance for surgery is there or not
• Adequate chemo therapy
• Ability to Achieve wide margin
Margins
– 3cm in bone
– At least one healthy muscle margin
– Barrier like physis, periosteum, thick fascia
– Focally close(marginal) for NVB acceptable
• Longevity of the implant is important: fixed hinge designs have high failure rate due to aseptic loosening (35% at 10 years) compared to rotating hinge with an HA coated collar (0% at 10 years)
LIMB SALVAGE SURGERY IN CHILDREN
• Main problem is limb length discrepancy
• So minimally invasive self-expandable prosthesis is used
ROTATIONPLASTY
• Procedure which allows the ankle to substitute as the knee after 1800 rotation of the limb
• Advantages
o Mobile and durable knee
o Gait better than above knee amputation
o Compensated for LLD
o Children adapt very well to the prosthesis
OUTCOME
• Survival is 60 to 70% with non-metastatic disease, 20 to 30% with metastatic disease
• 85% of relapses occur within first 3 years and 95% occur in first 5 years
• Local recurrence rate is <10%, most failures are in lungs
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